JPS62108871A - Production of oxazoles - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 5-cya/-4-methyl-oxazole, a more advanced intermediate.

Conventionally, this oxazole derivative is 5-lupamoyl-4
-Methyl-oxazole was prepared by reacting it with phosphorus 11 oxide while heating.3 However, this known method consists of the public fish, the porcelain oxazole, and the phosphorus 11 oxide.
This results in relatively low yields due to the carbonization that occurs.

A modification of this known method! i is 5-carbamoyl-4-7
The reaction between naruoxazole and Ii phosphorus oxide is carried out using a solvent, 1
111, in the presence of 1. The stability of quinoline recognized in ζ stability and the health benefits of quinoline to prevent discomfort
It has a harmful effect on the body. Furthermore, 111 of quinoline
Processing methods for producing ecologically unoccupied products from the raw and required phosphorus pentoxide are expensive and pose a series of technical problems. The reaction force of phosphorous pentoxide is an expensive and scarce raw material.

vinegar! Produce 5-cya/-4-methyl-oxazole in
A known method involves reacting 5-carbamoyl-4-methyl-oxazole with a lower alkanecarboxylic anhydride,
and release the reaction mixture or from it.
(lower alkali/carbamoyl)-4-methyl-
It consists of subjecting oxazole to thermal decomposition. However, the final thermal stage has certain drawbacks, such as particularly high processing temperatures, problems with the materials forming the reactor and the formation of products that are difficult to recycle.

Therefore, the first object of the present invention is to provide a method for producing 5-thia/-4-phthyloxazole in a simple and time-consuming manner, which makes it possible to produce 5-thia/-4-phthyloxazole in a simple and time-consuming manner. The above-mentioned drawbacks do not appear and the desired 5-cya/-4-methyl-oxazole is obtained in d'-yield and in good purity. This target is prepared according to the invention by starting from 5-(lower alkoxycarbonyl 4-methyl-oxazole and ammonia, and adding the starting materials in the > This is achieved by carrying out the reaction in the presence of a compound, but by isolating the 5-carbamoyl-4-methyl-oxazole formed as an intermediate and not treating it separately.

As lower flukoxycarbonyl radicals, in particular radicals are suitable in which the flufoxy radical has up to 6 carbon atoms and is straight-chain or branched. The lower flukoxycarbonyl group is preferably (C, ~, -flukoxy)carbonyl, especially ethoxycarbonyl.

Zorconium oxide or hafnium oxide catalysts can be present in essentially pure form, μ(1'#-), undiluted, or mixed with inert materials or supported on a carrier material.
! f, i.e. can be diluted. Examples of suitable inert or carrier materials are aluminum oxide and aluminum silicates. If the catalyst is diluted and the catalyst is diluted, the total weight of the catalyst is approximately 5 to 5% by weight of the vehicle.However, preferably the catalyst is diluted. In each case, the specific surface area of the undiluted or diluted catalyst is preferably at least 10 i/bi. ~90 seagulls 2/[1
By using dilute catalysts with a range of specific surface areas (depending on the density associated with the materials used), results of J&R are obtained.

The catalysts used according to the invention are partly commercially available or can be prepared by precipitating, for example, aqueous solutions of norconium oxychloride or hafnium oxychloride with ammonia, filtering, washing with water and drying in a manner known per se. It can be easily produced by grinding, sieving, forming into tablets, and calcining, for example at about 500-800'C (7). If the catalyst is to be diluted, it may be incorporated with an inert material or carrier material at any stage of such a process, but at the latest immediately after forming into tablets. 1j1j processing I11!l This method is especially suitable for comparison table L.
The value of the Ili product and at the same time the catalyst properties can be influenced by Jj.

Advantageous amounts of catalyst to use can be readily determined by those skilled in the art. In particular, this practice depends on the amounts of starting materials used, the reaction temperature and the type and size of the reactor.

5-(lower alkoxycarbonyl)-4 in the present invention
The reaction of -methyl-oxazole with ammonia is carried out using excess ammonia, and the molar ratio of ammonia oxazole is at least 1.5:1.

This ratio is preferably between 5:l and 10:l.

Further, the present invention is advantageously carried out at temperatures in the range of about 230-400°C, preferably between about 260°C and -1 mm:)50°C. Regarding the pressure at which the reaction is carried out, technical and
, the reaction is preferably carried out at atmospheric pressure of 1.

b-(+ttaalkoxycarbonyl)-4-methyl-
The oxazole is preferably introduced into a heated reactor in the form of a solution in a suitable solvent. Y luene is a particularly suitable solvent.

The reaction is also advantageously ignited under the addition of active gas, especially nitrogen.

The method according to the invention can be carried out in a continuous or batch manner,
Preferably, the reaction can be carried out continuously and advantageously in a packed bed reactor consisting of, for example, one or more thermal cuffs packed with catalyst. Tube heat exchangers are particularly suitable for production scales of 1 C. + of individual tubes
ft diameter and curvature are not critical. Advantageously, the deactivated catalyst is exposed to an oxygen-containing gas,
Preferably, t and diameter i are so that 1q can be generated by air.
1, R, 4J1 generation of catalyst by combustion of deposited coke is usually required after 100 to 200 hours m1 of use of the catalyst.

5-(lower alkoxycarbonyl)-4-methyl-oxazole 50-ZOOg/l catalyst volume/h (throughflow rate) is preferably introduced into the reactor. The ammonia, solvent and inert gas axes introduced into the filtration system are selected in such a way that the concentration of 5-(lower alkoxycarbonyl)-4-methyl-oxazole does not exceed 10 mol%.

The Jj method of the present invention produces the desired 5-anor 4-methyl-oxazole 41=- with high purity. Processing: 1. The t11 product is separated from the condensable oxazole and the water and alcohol formed during the reaction, preferably by cooling. Preferably, most of the wandering gas is reintroduced into the reactor. Then, the organic phase was separated from the resulting two-phase mixture and this was added to the 111th column.

The method of the present invention will be explained in more detail with reference to the following examples.

EXAMPLE 1 The reactor was enclosed by a tube furnace and was equipped with a vertically arranged glass tube (approximately 30 centimeters long, +
ff diameter of approximately 2C). The top and bottom of the glass tube are filled with ceramic and -X, and the middle part is filled with catalyst (:(
0 (to) l) was filled. A commercially available Norfuni oxide catalyst [Vershaw (l
lur5huw) Zr-Q: 1041'l as a catalyst''
(Using.

Adjust the R1 heat of the furnace to 310'C and IIL? Ti
5-ethoxycarbonyl-4- in lx reaction 4 per liter
18+1 of 25 talo solution of methyl-oxazole, 71 of ammonia and 7e of nitrogen were introduced. The reaction product was condensed in a condenser and analyzed by chromatography.

With a conversion rate of 99%, the II'i rate of 5-noano-4-methyl-oxazole was 78%.

Example 2 Using stearic acid (1% by weight) as a lubricant, the tablets (3 Calcined commercially available zirconium oxide powder] Guinamit・/-Bell (Llyna
+aiL Nobel) Guinanorcon"'l" (
1) 7.1 Ω was used as a catalyst for reactor 1.

Using this catalyst, the yield of -C15-na7-4-methyl-oxazole was 75% with a conversion rate of 99%.
child.

Example 3 Zirconium oxide prepared from zirconium nitrate was used as a catalyst in the reactor 1 described in Example 1. Methyl-
Ii'1.1% of oxazole was 74%.

The catalyst used was prepared as follows: Zirconium nitrate pentahydrate 500% in 2.51% distilled water
To the stirred solution of ml of microcrystalline cellulose 1 ml of Avicel pH 1011 + 5 + B and V 25% aqueous ammonia: tlOu + 1 was added. The precipitate was filtered off with suction, washed with distilled water and calcined at 700° C. for 3 hours. Next, the resulting powdered zirconium oxide was mixed with 4% by weight of stearic acid (lubricating) to form tablets.
, 6++++o, l'7.2 :l++++n), 5
00℃ 1: (Heated at 181 hours.

Example 4 Large IM of norphnium oxide produced from norconyl chloride
The reactor described in Example 1 was used as a catalyst. The conversion was 99%, and the yield of 5-cyano-4-methyl-oxazole was 81%.

The catalyst used was prepared as follows: M f11 norphnyl chloride hexahydrate 3 in 1.1 l water
Graphite 251 (and 200 l of 25% ammonia water) was added to the stirred mixture at 97°C.
611. 'r1111 Dry and form 1 tablet l(
r4'l3+o+n, thickness 2.2+nm), 7
00°C: Power calcined for 1 hour.

Example 5 A norconium oxide catalyst prepared by aluminum oxide was used in the reactor described in Example 1, and the temperature was set to: +
The temperature was adjusted to 20 c:. I'm going to turn into a 100% j-'C
1 parent car of 15-Synopsis 4-Menal-Oxazole is 7
It was 6%.

The catalyst used was prepared as follows: γ-7 Lumina
731+) 70H was heated to 1ooO'c for 1b hours,
It was then impregnated with 40.5% of zirconium chain acid pentahydrate in 40.5wN of distilled water. After a death, this thing is 200
The tube was heated to 450'C within 5 hours while passing a η-air stream at a rate of N/Lν, then 111! This temperature was maintained until no more nitric acid evolved. The coating of zirconium oxide on the catalyst thus produced is 1
It was 5%.

Example 6 An oxidized hafram catalyst prepared from hafram oxychloride was used in the reactor described in Example 1. With a conversion rate of 98%, the yield of 5-na-7-4-methyl-oxazole was 98%.

The catalyst used was prepared as follows: A distilled water 1.4
To a stirred solution of 11' hafnium oxychloride octahydrate, 500 ml of 5% aqueous ammonia was added. The precipitate was filtered off with suction, washed with distilled water, and diluted with l:jOoC.
The mixture was dried for 16 hours at 600'C, combined with 1u6 of stearin 11ifth, formed into tablets, and calcined at 600'C for 13 hours.

Example 7 A zirconium oxide catalyst coated on aluminum silicate was used in the reactor described in Example 1, with the furnace temperature at 350°C.
The temperature was adjusted to ℃. With a conversion rate of 98%, 5-dia2-4
The yield of -methyl-oxazole was approximately 55%.

The catalyst used was as described in Example 5, except that instead of the aluminum oxide support, an aluminum silicate support [Fulton (Nort.
on) SA 32:12] was manufactured using J11.

In this case, the coating of zirconium oxide on the catalyst thus prepared was 9.3%.9 Example 8 A zirconium oxide catalyst prepared from zirconium 1-pyrate was used in the reactor described in Example 1. IA $
The yield of 5-enano-4-7thyl-oasazole was about 81%.

The catalyst used was prepared as follows: Zirconium carbide in 50 Iol of distilled water: 125n+1 solution.

The resulting mixture was evaporated in a rotary evaporator and the remaining lh was
5 (Dry at 1°C for 161 hours. Combine the resulting powdered oxidized norconinent with stearic acid,
I'i'l Iko#ll: II;shi,70()"C
-('l11.'/Opened and calcined.

'Examples 9-14 The horn method described in Example I was repeated using different ammonia and nitrogen passage rates. It is clear from the results of this experiment that the yield depends on these passing rates, and the results in Table 11 are included in Table 1.

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Claims (1)

[Claims] 1,5-(lower alkoxycarbonyl)-4-methyl-
A process for producing 5-cyano-4-methyl-oxazole, characterized in that the oxazole is reacted with ammonia in the gas phase in the presence of a zirconium oxide or hafnium oxide catalyst. 2,5-(lower alkoxycarbonyl)-4-methyl-
2. The method according to claim 1, wherein 5-ethoxycarbonyl-4-methyl-oxazole is used as the oxazole. 3. The method according to claim 1 or 2, wherein the specific surface area of the undiluted or diluted catalyst is at least 10 m^2/g. 4. A process according to any one of claims 1 to 3, wherein the molar ratio of ammonia:5-(lower alkoxycarbonyl)-4-methyl-oxazole in the reaction is at least 1.5:1. 5. The method according to claim 4, wherein the molar ratio is 5:1 to 10:1. 6. The method according to any one of claims 1 to 5, wherein the reaction is carried out at a temperature range of 230°C to 400°C. 7. The method according to claim 6, wherein the reaction is carried out at a temperature range of 260°C to 350°C. 8,5-(lower alkoxycarbonyl)-4-methyl-
8. A process according to any one of claims 1 to 7, wherein the oxazole is introduced into the heated reactor in solution in toluene.